Nitric oxide synthase and nitric oxide production in in vivo-derived mast cells

Abstract

Nitric oxide (NO) is a potent mediator synthesized by a variety of cells involved in inflammatory reactions. We investigated the expression of NO synthase (NOS) in rat peritoneal mast cells (PMC). Small amounts of eNOS mRNA were detected basally, whereas neither mRNA for iNOS nor nNOS was detected in unstimulated PMC. Following stimulation by antigen, interferon-γ (IFN-γ), or anti-CD8 antibody, PMC up-regulated iNOS mRNA expression. In situ RT-PCR confirmed that iNOS mRNA originated from PMC. Production of iNOS protein was confirmed in stimulated PMC by immunohistochemistry. Upon stimulation with antigen, IFN-γ, or anti-CD8, nitrite production was increased significantly (8.4±0.6, 7.6±0.9, and 6.6±0.9 μM/2×105 cells/48 h NO2−, respectively; P<0.01), whereas unstimulated PMC released 2.1 ± 0.3 μM/2 × 105 cells/48 h NO2−. These findings demonstrate that in vivo-derived PMC transcribe and translate mRNA for NOS and produce NO.

Microcirculatory dysfunction during intestinal ischemia-reperfusion

“…Many immune cells, including leukocytes and MCs, are capable of NO production under both physiologic and pathophysiologic conditions (3,37,50,84,121). The connection between endothelial cell-derived NO and the activation of intestinal MCs has raised the possibility that endogenous NO acts as a homeostatic depressor of MC reactivity that otherwise leads to leukocyte recruitment.…”